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In our study we comprehensively characterized 488 melanoma cases from 451 non\u2010<jats:italic>CDKN2A\/CDK4<\/jats:italic> families for mutations in 30 established and candidate melanoma susceptibility genes using a custom\u2010designed targeted gene panel approach. We identified (likely) pathogenic variants in established melanoma susceptibility genes in 18 families (<jats:italic>n<\/jats:italic> = 3 <jats:italic>BAP1<\/jats:italic>, <jats:italic>n<\/jats:italic> = 15 <jats:italic>MITF<\/jats:italic> p.E318K; diagnostic yield 4.0%). Among the three identified <jats:italic>BAP1<\/jats:italic>\u2010families, there were no reported diagnoses of uveal melanoma or malignant mesothelioma. We additionally identified two potentially deleterious missense variants in the telomere maintenance genes <jats:italic>ACD<\/jats:italic> and <jats:italic>TERF2IP<\/jats:italic>, but none in the <jats:italic>POT1<\/jats:italic> gene. <jats:italic>MC1R<\/jats:italic> risk variants were strongly enriched in our familial melanoma cohort compared to healthy controls (R variants: OR 3.67, 95% CI 2.88\u20134.68, <jats:italic>p<\/jats:italic> &lt;0.001). Several variants of interest were also identified in candidate melanoma susceptibility genes, in particular rare (pathogenic) variants in the albinism gene <jats:italic>OCA2<\/jats:italic> were repeatedly found. We conclude that multigene panel testing for familial melanoma is appropriate considering the additional 4% diagnostic yield in non\u2010<jats:italic>CDKN2A\/CDK4<\/jats:italic> families. Our study shows that <jats:italic>BAP1<\/jats:italic> and <jats:italic>MITF<\/jats:italic> are important genes to be included in such a diagnostic test.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ijc.31984","type":"journal-article","created":{"date-parts":[[2018,11,10]],"date-time":"2018-11-10T16:33:37Z","timestamp":1541867617000},"page":"2453-2464","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Multigene panel sequencing of established and candidate melanoma susceptibility genes in a large cohort of Dutch non\u2010<i>CDKN2A\/CDK4<\/i> melanoma families"],"prefix":"10.1002","volume":"144","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3831-6022","authenticated-orcid":false,"given":"Thomas P.","family":"Potjer","sequence":"first","affiliation":[{"name":"Department of Clinical Genetics Leiden University Medical Centre  Leiden the 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